Racemic phenylalanine is a compound in which L-phenylalanine and D-phenylalanine are mixed in equal amounts. Their physical and chemical properties are basically the same, but their optical activity is opposite to each other. Therefore, it is difficult to separate the racemate into phenylalanine with a single configuration by general physical methods, and a special method must be used for separation. Using 3,5-dinitrobenzoyl substituted β-cyclodextrin as the stationary phase, chiral thin-layer chromatography was used to resolve D, L-amino acids. It was found that phenylalanine was due to the existence of the benzene ring structure The strong interaction with the chiral stationary phase makes the racemic phenylalanine have different physical properties, so a better resolution effect is obtained. However, the resolution agent used in this method is expensive, consumes a lot, and the resolution efficiency is not high, so it is difficult to prepare for large-scale production and use. Penicillin acylase was immobilized, and then the racemic phenylalanine derivative N-phenylacetyl-D, L-phenylalanine was resolved to obtain the crude product N-phenylacetyl-D-phenylalanine, which was purified by water The protection group was removed, and then the cationic resin exchange desalting treatment was used to obtain D-phenylalanine with an optical purity of 91.4% and a yield of 67%. This method also has the disadvantages of low efficiency, high energy consumption, low yield, and low optical purity of the product. There are also related literature reports that racemic phenylalanine is resolved with chemical reagent dioxaphosphorinane compounds, but the resolution rate is less than 36%.
Due to the characteristics of relatively mild reaction conditions and high stereoselectivity, biological methods have been widely concerned and highly valued in the field of amino acid production. There are also many literature reports on the production of D-phenylalanine by biological methods. D-configuration amino acid acylase was induced from two special bacteria, and N-acetyl-D-phenylalanine could be converted into D-phenylalanine by using this enzyme, with the highest yield reaching 83.1%. The optical purity of the product has not been reported. Although this method is feasible, it is limited to laboratory research and does not have the conditions for industrial production. According to relevant reports, the Japanese Nakamoto Chemical Co., Ltd. recombined D-hydantoinase and N-carbamoylamino gene into E. coli through genetic engineering and successfully expressed it, and extracted the crude enzyme for immobilization to produce D-phenylalanine. Good experimental results have been obtained. At present, companies such as Nakamoto Chemical in Japan have improved the strains through genetic engineering, but there are still shortcomings such as low substrate concentration, long conversion time, and low conversion rate in the production of D-phenylalanine.
Asymmetric synthesis generally refers to a class of reactions that use special chemical reagents, solvents, catalysts, or physical factors to convert latent chiral units into chiral units, thereby producing unequal amounts of stereoisomeric products. The asymmetric synthesis reaction has developed very rapidly in recent years, with remarkable achievements, and has become one of the most active research fields in organic chemistry. There are also many reports on the synthesis of phenylalanine using this method. In 1988, it was reported that D-camphor ketimine, which was condensed with D-camphor and glycine butyl ester, was used as a chiral synthon, and D-phenylalanine was synthesized by enantioselective method through asymmetric synthesis. The optical purity and The ee value reached 95%, and the yield reached 92.7%. However, this method requires relatively harsh reaction conditions, high energy consumption, and high cost, and is only suitable for small-scale synthesis research in laboratories. Another efficient method for the asymmetric synthesis of α-amino acids is the use of rhodium-catalyzed tandem 1,4-addition protonations (Michael-type addition reactions) to catalyze α,β-dehydroamino acids. Using organometallic reagents to react amidoacrylic acid esters in the presence of rhodium catalysts and chiral phosphine ligands to obtain corresponding α-chiral amino acid derivatives. The ee value of the phenylalanine derivative was 89.5% and it was in the L configuration. The method is simple to operate, but the reaction uses too much rhodium catalyst and chiral phosphine ligand, the cost is too high and the optical purity of the product is not high, and it only stays in the laboratory research stage, and no production report uses this method.
